1. 항 파킨슨씨 약물
Anti-Parkinson Drug

2. 파킨슨씨병 의 날
4월 11일

4. Substansia Nigra
(흑질)

5. History of Parkinson’s Disease
Parkinon’s small but famous publication, "Essay on the Shaking Palsy", appeared in 1817, 7 years before his death in 1824.

6. Epidemiology Average incidence is 20 per 100,000 in North America
1 Million affected in the United States
50,000 new cases per year
Cost estimated to exceed $5.6 Billion annually

7. Four Typical Signs of Parkinsonism
Diagnostic Features
Four Cardinal Signs
Tremor
Rigidity
Akinesia and bradykinesia
Postural instability
Four Typical Signs of Parkinsonism

8. Reduction of inhibitory Dopaminergic Neron
Parkinson’s Disease
Reduction of inhibitory Dopaminergic Neron
Imbalance of Ach & DA
Pakinson Syndrome

9. Positron-Emission Tomography

11. Antiparkinson’s Drug Treatment for Parkinson’s disease
Pakinson syndrome
Dopamine receptor agonist
DA Synthesis
MAO-B inhibitor
Anti-Muscarinic agent

12. Parkinson’s disease 예방

13. 담배와 파킨슨씨병

14. Drug Interaction

16. Structure of Drug for Parkinson’s Disease

17. Why L-Dopa instead of DA?
If dopamine is too polar to cross the BBB, how can L-DOPA cross it?

18. Trojan horse Approach for Carrier Protein
Recognized as amino acid by carrier protein

21. The Effect of Carbidopa on the metabolism of L-Dopa

22. The Action of Selegiline in the metabolism of Dopamine

23. The mechanism of Entacaone as Anti-parkinsonism

24. Muscarine Antagonist ☞ Chemical Name:
3-(1-Piperidyl)-1-cyclohexyl-1-phenyl-1-propanol HCl
a-Cyclphexyl-a-phenyl-1-piperidinepropanol HCl
☞ Trade Name:
트리헥산 정 (태극), 염산트리헥시딜 정 (장우), Artane® (Lederle) 24

25. Retrosynthesis of Trihexylphenidyl

26. Muscarine Antagonist ☞ Chemical Name:
:1-(Bicyclo[2.2.1]hept-5-en-2-yl-1-phenyl-3-phenyl-3-(piperidin yl)propan-1-ol HCl
:a-(2-Norbonenyl)-a-pheny-1-piperidinepropanol HCl
☞ Trade Name:
아톨 정 (유나이티드), 염산비페리덴 정 (풍림), Akineton® (Abbot)

27. Muscarine Antagonist

28. Mannich Reaction

29. Dopamine Agonist ☞ Chemical Name:
:(S)-2-Amino-3-(3,4-dihydroxyphenyl)propanic acid
☞ Trade Name:
레보다 서방정 (산도스), 스다레보 필름코팅 정 (노바티스), 씨네메트/씨알정 (MSD), 콤비도파 서방정(노바티스) Stalevo® (a mixture of L-DOPA, carbidopa, entacapone, Orion

30. Side Effect of levodopa

31. Drug Interactions

35. Why L-Dopa, not Dopamine ?
Not cross the BBB
Cross the BBB
In Brain

36. Retro synthesis of L-DOPA
L-Tyrosine

37. L-DOPA

39. Regiochemistry of Bayer-Villiger-Oxidation

40. Retrosyntheis of L-DOPA(II)

41. L-DOPA (Dopamine Agonist)

42. Carbidopa ☞ Chemical Name:
:(S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid
☞ Trade Name:
: Stalevo® (a mixture of L-DOPA, carbidopa, entacapone, Orion

43. Levodopa & Carbidopa
Nausea and Vomiting

44. Retrosynthesis of Carbidopa

45. Dopamine Agonist

46. Dopamine Agonist

47. Dopamine Agonist

48. Dopamine Agonist Ropinirole ☞ Chemical Name:
4-[2-(Dipropylamino)ethyl-1,3-dihydro-2H-indol-2-one
☞ Trade Name:
: RopiniroleHCl: 뉴큅 정 (유한), 로큅 정 (대웅), 로피맥스 전 (고려), 파로킨 정 (현대), 도파로핀(일동), 로킨스 정(신풍). 리큅피디 정 (글라고스미스클라인)
: Ropinirole: 리큅 정 (글락소스미스클라인, ropinirole), Requip (GSK)

52. Retrosynthesis of ropiniroleOH

53. Synthesis of Ropinirole
Dopamine Agonist
Synthesis of Ropinirole

54. selegiline (R)-N-methyl-N-(1-phenylpropan-2-yn)-1-amine
유멕스 정(사노피-아벤티스 코리아), 아오비 정(초당), Eldepryl(Somerset)

56. Retrosynthesis of Selegiline

57. Synthesis of Selegiline
Dopamine Agonist
Synthesis of Selegiline

58. Asymmetric Synthesis of Selegiline
Dopamine Agonist
Asymmetric Synthesis of Selegiline

59. Entacapone Dopamine Agonist ☞ Chemical Name:
(E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)-propenamide
☞ Trade Name:
: 콤탄 정 (노바티스), 스타레보 필름코팅 정 (L-DOPA 및 Carbidopa 와 복합제, 노바티 스), Comtan® (Orion)

61. Retrosynthesis of Entacapone

62. Synthesis of Entacapone
Dopamine Agonist
Synthesis of Entacapone